Detection of Tumor Cell-Induced Platelet Aggregation and Granule Secretion

Hematogenous metastatic spread of cancer is strongly dependent on and triggered by an intensive interplay of tumor cells with platelets. Immediately after entering the blood vascular system, tumor cells are surrounded by a platelet cloak, which protects them physically from shear stress and from attacks by the immune surveillance. Furthermore, tumor cell binding activates platelets, which in turn release growth factors and chemokines to recruit myeloid cells into the platelet/tumor cell microemboli, eventually create a permissive microenvironment in the early metastatic niche. Although the molecular mechanisms of tumor cells to activate platelets appear versatile being a matter of further research, interference with platelet activation turns out to be an attractive target to efficiently inhibit tumor metastasis. Some experimental assays are generally recognized to follow tumor cell-induced platelet activation (TCIPA), which provide an insight into the molecular mechanisms of TCIPA and allow searching for potential inhibitors. In this chapter, we describe the two most prominent experimental assays to follow TCIPA, namely platelet aggregation and platelet granule secretion, experimentally realized by dense granules´ ATP quantification. Although light transmission aggregometry and ATP detection from dense granule secretion are two age-old techniques, they are still highly relevant to provide reliable information concerning platelet activation status since all tumor cell-derived molecular triggers are covered and monitored in the experimental outcome.